|Margolis, Lee - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Rivas, Donato - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Berrone, Maria - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Ezzyat, Yassine - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Young, Andrew - Us Army Research|
|Mcclung, James - Us Army Research|
|Fielding, Roger - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Pasiakos, Stefan - Us Army Research|
Submitted to: Frontiers in Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/20/2016
Publication Date: 10/5/2016
Citation: Margolis, L., Rivas, D.A., Berrone, M., Ezzyat, Y., Young, A.J., McClung, J.P., Fielding, R.A., Pasiakos, S.M. 2016. Prolonged calorie restriction downregulates skeletal muscle mTORC1 signaling independent of dietary protein intake and associated microRNA expression. Frontiers in Physiology. https://doi.org/10.3389/fphys.2016.00445.
DOI: https://doi.org/10.3389/fphys.2016.00445 Interpretive Summary: Short-term (5-10 day) calorie restriction (CR) reduces muscle protein synthesis, and consuming a diet higher in protein can prevent this decline in protein synthesis. It is thought that dietary protein has this effect by stimulating a key regulatory protein in muscle called mTORC1, which controls protein synthesis in muscle. In the present study, we used a rodent animal model to determine the effects of CR and a high protein diet on mTORC1 function. We found that CR reduced muscle protein content and also decreased mTORC1 activity. This response was not different between the group receiving high or low protein intake. The study demonstrates that CR affects muscle protein content by reducing the activity of the protein mTORC1 and that this effect is not modified by differences in dietary protein intake.
Technical Abstract: Short-term (5-10 days) calorie restriction (CR) downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1), however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR). Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or calorie restricted (CR; 40%) adequate (10%, AIN-93M) or high (32%) protein milk-based diets for 16 weeks. Body composition was determined using dual energy X-ray absorptiometry and muscle protein content was calculated from muscle homogenate protein concentrations expressed relative to fat-free mass to estimate protein content. Western blot and RT-qPCR were used to determine mTORC1 signaling and mRNA and miR expression in fasted mixed gastrocnemius. Independent of dietary protein intake, muscle protein content was 38% lower (P < 0.05) in CR compared to AL. Phosphorylation and total Akt, mTOR, rpS6, and p70S6K were lower (P < 0.05) in CR vs. AL, and total rpS6 was associated with muscle protein content (r = 0.64, r2 = 0.36). Skeletal muscle miR expression was not altered by either energy or protein intake. This study provides evidence that chronic CR attenuates muscle protein content by downregulating mTORC1 signaling. This response is independent of skeletal muscle miR and dietary protein.